Abstract Conventional suture ligation of vascular tissues during surgery is time consuming and skill intensive. Use of energy-based devices enables more rapid and efficient vessel and tissue ligation to maintain hemostasis during surgery than standard sutures and mechanical clips, which leave foreign objects in the body and disrupt the procedure through the need to exchange instruments. Ultrasonic (US) and radiofrequency (RF) energy- based devices expedite a number of labor-intensive surgical procedures, including lobectomy, nephrectomy, gastric bypass, splenectomy, thyroidectomy, hysterectomy, and colectomy, with significant cost savings. However, both RF and US devices have limitations, including potential for undesirable charring and unnecessarily large collateral thermal damage zones, with thermal spread averaging greater than 1 mm. A major concern is the possibility of unintended thermal damage to adjacent critical tissue structures when performing delicate procedures in confined spaces. Additionally, the active jaw of US devices can reach temperatures in excess of 200 oC during an application and can take greater than 20 s to cool to usable temperatures before proceeding with further applications. The maximum temperatures on the active jaw of RF devices are lower (< 100 oC), but larger thermal spread is observed. Over the past 8 years, our laboratory has been developing a novel alternative method using infrared (IR) lasers for vessel sealing. Several advantages of laser-based sealing and cutting of vascular tissues compared to conventional US and RF energy-based devices include: (1) More rapid sealing and cutting of vascular tissues with seal and cut times as short as 1 s each; (2) More directed deposition of energy into tissue with collateral thermal spread of less than 1 mm; (3) Stronger vessel seals with higher burst pressures (up to 1500 mmHg); (4) An integrated device capable of optical sealing and cutting of vascular tissues without the need for a deployable mechanical blade to bisect tissue seals; (5) Safer profile with lower jaw peak temperatures (< 60 oC) compared to ultrasound (~ 200 oC) and radiofrequency (~ 100 oC) devices; (6) Sealing of large blood vessels greater than 5 mm. However, several fundamental questions remain concerning our basic understanding of the laser-tissue interactions mechanism and feasibility of our method before it can be adopted in the clinic. The following specific aims intend to answer these basic questions, thus facilitating optimization of the laser parameters and device design for sealing of vascular tissues: (1) Optical and thermal property measurements of blood vessels as a function of composition (collagen/elastin ratio), temperature, and pressure; (2) Design and testing of laparoscopic vessel sealing device, integrating optical diagnostics for confirming successful vessel closure and avoiding damage to adjacent tissue structures (e.g. nerves); (3) Direct comparison between laser, US, and RF devices in an in vivo acute pig model, to determine sealing and cutting times and quantify collateral thermal damage.